Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Objectives: . This study evaluates the enduring efficacy and patient satisfaction of dupilumab with interdose interval adjustments based on the Sino-Nasal Outcome Test (SNOT-22) in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: . A retrospective analysis was conducted on 44 patients who had been treated with dupilumab for over 6 months. This study targeted individuals diagnosed with CRSwNP according to the 2020 edition of the European Position Paper on Rhinosinusitis and Nasal Polyps Criteria. The treatment involved an add-on dupilumab regimen, where the interdose interval was adjusted based on the SNOT-22 scores. Dosage adjustments were made such that patients with initial SNOT-22 scores greater than 40 were tapered to a target level of 20 or less. Similarly, for patients with initial scores of 40 or less, the treatment aimed for an improvement of 50% or more. At each visit, the effectiveness of the treatment was evaluated using SNOT-22, nasal polyp scores (NPS), and a subjective satisfaction questionnaire adapted from the Treatment Satisfaction Questionnaire for Medication (TSQM v.1.4). Results: . The adjustment of the interdose interval for dupilumab based on SNOT-22 scores demonstrated sustained improvements in patients’ subjective symptoms, satisfaction, and NPS. The mean (standard deviation) SNOT-22 scores significantly decreased from 46.04 (22.30) to 14.72 (13.66) over 6 months (P<0.001). Similarly, NPS scores improved from 3.20 (2.24) to 1.72 (1.46) within the same period (P<0.001). Satisfaction scores, ranging from 0 to 5, consistently remained above 3.5 for up to 6 months (P=0.166). Additionally, there was a significant correlation between the improvement in the nasal symptom domain of the SNOT-22 scores and higher satisfaction scores. Conclusion . Adjusting dupilumab dosing intervals based on SNOT-22 scores from the outset resulted in sustained efficacy and patient satisfaction in Korean patients with CRSwNP. This approach will meaningfully assist clinicians in determining the optimal dupilumab dosing interval.

Objectives: . This study evaluates the enduring efficacy and patient satisfaction of dupilumab with interdose interval adjustments based on the Sino-Nasal Outcome Test (SNOT-22) in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: . A retrospective analysis was conducted on 44 patients who had been treated with dupilumab for over 6 months. This study targeted individuals diagnosed with CRSwNP according to the 2020 edition of the European Position Paper on Rhinosinusitis and Nasal Polyps Criteria. The treatment involved an add-on dupilumab regimen, where the interdose interval was adjusted based on the SNOT-22 scores. Dosage adjustments were made such that patients with initial SNOT-22 scores greater than 40 were tapered to a target level of 20 or less. Similarly, for patients with initial scores of 40 or less, the treatment aimed for an improvement of 50% or more. At each visit, the effectiveness of the treatment was evaluated using SNOT-22, nasal polyp scores (NPS), and a subjective satisfaction questionnaire adapted from the Treatment Satisfaction Questionnaire for Medication (TSQM v.1.4). Results: . The adjustment of the interdose interval for dupilumab based on SNOT-22 scores demonstrated sustained improvements in patients’ subjective symptoms, satisfaction, and NPS. The mean (standard deviation) SNOT-22 scores significantly decreased from 46.04 (22.30) to 14.72 (13.66) over 6 months (P<0.001). Similarly, NPS scores improved from 3.20 (2.24) to 1.72 (1.46) within the same period (P<0.001). Satisfaction scores, ranging from 0 to 5, consistently remained above 3.5 for up to 6 months (P=0.166). Additionally, there was a significant correlation between the improvement in the nasal symptom domain of the SNOT-22 scores and higher satisfaction scores. Conclusion . Adjusting dupilumab dosing intervals based on SNOT-22 scores from the outset resulted in sustained efficacy and patient satisfaction in Korean patients with CRSwNP. This approach will meaningfully assist clinicians in determining the optimal dupilumab dosing interval.

Objectives: . This study evaluates the enduring efficacy and patient satisfaction of dupilumab with interdose interval adjustments based on the Sino-Nasal Outcome Test (SNOT-22) in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: . A retrospective analysis was conducted on 44 patients who had been treated with dupilumab for over 6 months. This study targeted individuals diagnosed with CRSwNP according to the 2020 edition of the European Position Paper on Rhinosinusitis and Nasal Polyps Criteria. The treatment involved an add-on dupilumab regimen, where the interdose interval was adjusted based on the SNOT-22 scores. Dosage adjustments were made such that patients with initial SNOT-22 scores greater than 40 were tapered to a target level of 20 or less. Similarly, for patients with initial scores of 40 or less, the treatment aimed for an improvement of 50% or more. At each visit, the effectiveness of the treatment was evaluated using SNOT-22, nasal polyp scores (NPS), and a subjective satisfaction questionnaire adapted from the Treatment Satisfaction Questionnaire for Medication (TSQM v.1.4). Results: . The adjustment of the interdose interval for dupilumab based on SNOT-22 scores demonstrated sustained improvements in patients’ subjective symptoms, satisfaction, and NPS. The mean (standard deviation) SNOT-22 scores significantly decreased from 46.04 (22.30) to 14.72 (13.66) over 6 months (P<0.001). Similarly, NPS scores improved from 3.20 (2.24) to 1.72 (1.46) within the same period (P<0.001). Satisfaction scores, ranging from 0 to 5, consistently remained above 3.5 for up to 6 months (P=0.166). Additionally, there was a significant correlation between the improvement in the nasal symptom domain of the SNOT-22 scores and higher satisfaction scores. Conclusion . Adjusting dupilumab dosing intervals based on SNOT-22 scores from the outset resulted in sustained efficacy and patient satisfaction in Korean patients with CRSwNP. This approach will meaningfully assist clinicians in determining the optimal dupilumab dosing interval.

Pulmonary vein isolation is an well-established treatment strategy for atrial fibrillation (AF), and it is especially effective for patients with paroxysmal AF. However, the success rate is limited for patients with persistent AF, because non-pul‑ monary vein triggers which increase AF recurrence are frequently found in these patients. The major non-pulmonary vein triggers are from the left atrial posterior wall, left atrial appendage, ligament of Marshall, coronary sinus, superior vena cava, and crista terminalis, but other atrial sites can also generate AF triggers. All these sites have been known to contain atrial myocytes with potential arrhythmogenic electrical activity. The prevalence and clinical characteristics of these non-pulmonary vein triggers are well studied; however, the clinical outcome of catheter ablation for persistent AF is still unclear. Here, we reviewed the current ablation strategies for persistent AF and the clinical implications of major non-pulmonary vein triggers.

METHODS: The efficiency of electroporation-based delivery of AsCpf1/mRNA and AsCpf1/RNP to target exon 3 of leukemia inhibitory factor (Lif) into mouse zygotes was evaluated. Embryos that developed to the two-cell stage after zygote electroporation were transferred into the oviducts of surrogate mothers to produce AsCpf1-mediated LIF KO mice. The genome editing efficiency of blastocysts and pups was tested using the T7E1 assay and/or DNA sequencing. Congenital abnormalities and reproductive phenotypes in LIF KO mice produced by electroporation with AsCpf1/RNP were examined. RESULTS: Survival and two-cell development of electroporated zygotes were comparable between the AsCpf1/mRNA and AsCpf1/RNP groups, whereas genome editing efficiency was relatively higher in the AsCpf1/RNP group (13.3% vs 18.1% at blastocyst and 33.3% vs 45.5% at offspring), respectively. Two mouse lines with a frameshift mutation in exon 3 of the Lif gene were established from the AsCpf1/RNP group. All congenital abnormalities of LIF KO mice produced by AsCpf1/RNP electroporation were observed. AsCpf1-mediated LIF KO mice showed postnatal growth retardation and implantation failure, both of which are major phenotypes of LIF KO mice generated by conventional gene targeting. CONCLUSION Electroporation of AsCpf1/RNP at the zygote stage is an efficient genome editing method to produce KO mice.